Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the earliest events in mammalian embryogenesis is the formation of the inner cell mass (ICM) and the subsequent delamination of primitive endoderm. We have found that mRNA for fibroblast growth factor (FGF)-4, but not FGF-3, is expressed in preimplantation mouse blastocysts and that the FGF-4 polypeptide is present in ICM cells. ICM-like embryonal carcinoma cells and embryonic stem cells also express FGF-4. Conversely, differentiated embryonal carcinoma cells in the endoderm lineage express FGF-3, but not FGF-4 mRNA. Although mouse embryos expressed FGF-4 mRNA from the 1-cell stage, embryos cultured from the 2-cell through the blastocyst stage in the presence of recombinant FGF-4 did not respond mitogenically. However, when ICMs that were isolated by immunosurgery were cultured with FGF-4, the number of morphologically distinct, differentiated parietal endoderm cells growing out onto the coverslip increased, without an increase in the number of undifferentiated ICM cells. ICM outgrowths cultured with FGF-4 increased their secretion of 92 x 10(3) M(r) gelatinase and tissue plasminogen activator, a hallmark of migrating cells. Receptors for FGF-4 (FGFR-3 and FGFR-4) are expressed in all cells of the mouse blastocyst. These findings indicate that FGF-4 produced by undifferentiated ICM cells acts in the peri-implantation period of embryogenesis to influence the production and behavior of endoderm cells derived from them.
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PMID:Expression and function of FGF-4 in peri-implantation development in mouse embryos. 792 26

The intraovarian mechanisms for follicle recruitment, growth, maturation, and ovulation are not well understood. The data suggest that fibroblast growth factor (FGF)-2 is expressed in granulosa and theca cells of growing and mature follicles and in luteal cells during pregnancy. Exogenous FGF-2 modulates steroidogenesis, stimulates tissue plasminogen activator (tPA), and induces germinal vesicle breakdown (GVBD) in cultured follicles. Previously, we have reported that another FGF ligand, FGF-4, is expressed in ovulated mouse oocytes. Two studies have examined the expression of receptors (FGFR) for FGF ligands in the ovary. These prior reports have been limited to FGFR-1, one of the four isoforms that are variably expressed in adult mammalian tissues. This study evaluates FGFR-4 and FGFR-3 mRNA expression in the ovary. Granulosa cells from several follicular stages express the receptor for FGFR-4 mRNA as assayed by in situ hybridization. FGFR-4 mRNA is not expressed in theca cells or the oocyte. FGFR-3 mRNA is not detected in the ovary by in situ hybridization. These results suggest that FGFR-4 may play a role in mediating the effects of FGF ligands in follicular development in the ovary.
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PMID:Fibroblast growth factor receptor (FGFR)-4, but not FGFR-3 is expressed in the pregnant ovary. 932 58

In breast stroma urokinase plasminogen activator (uPA) is predominantly expressed by fibroblasts located in the near vicinity of tumor cells, and fibroblast-derived insulin-like growth factor-1 (IGF-1) may be involved in inhibiting the expression of uPA in these fibroblasts. To investigate a possible role for fibroblast growth factors (FGFs), we evaluated the expression of components of the PA system and the IGF system in normal and tumor-tissue-derived human breast fibroblasts exposed to various FGFs in vitro. mRNA analysis revealed that FGF-1, FGF-2 and FGF-4 induced the mRNA expression levels of uPA, tPA, uPAR, PAI-1 and PAI-2, and reduced those of IGF-1, IGF-1R, IGF-2R and IGFBP-4, without significantly affecting the levels of IGFBP-3, IGFBP-5 and IGFBP-6 mRNA. Concerning the expression of IGF-2 mRNA, the effects mediated by FGF-1, FGF-2 and FGF-4 were divergent. In general, the effects elicited by FGF-1 on the various mRNA levels studied were rapid and short-term. Those mediated by FGF-2 overall lagged behind but were longer-lasting. For FGF-4 an in between pattern was observed. Blocking transcription and translation demonstrated that a) both the FGF-1 and FGF-2 induced effects were the result of altered gene transcription or mRNA stability, b) the short-term effects mediated by FGF-1 and FGF-2 required de novo protein synthesis, and c) the long-term effects elicited by FGF-2 did not depend on de novo protein synthesis during the first 24 h, but were triggered by proteins produced or made available thereafter. The data presented propose that of the FGFs studied (FGF-1, -2, -4, -5, and -7), FGF-2 is the most attractive target for therapeutical strategies aimed at diminishing the contribution of stromal fibroblasts in the PA-directed breast tumor proteolysis.
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PMID:Differential effects of fibroblast growth factors on expression of genes of the plasminogen activator and insulin-like growth factor systems by human breast fibroblasts. 1200 51